Aharonov and Bohm versus Welsh eigenvalues.

We consider a class of two-dimensional Schrödinger operator with a singular interaction of the δ type and a fixed strength ß supported by an infinite family of concentric, equidistantly spaced circles, and discuss what happens below the essential spectrum when the system is amended by an Aharonov-Bohm flux α∈[0,12] in the center. It is shown that if ß≠0 , there is a critical value αcrit∈(0,12) such that the discrete spectrum has an accumulation point when α<αcrit , while for α≥αcrit the number of eigenvalues is at most finite, in particular, the discrete spectrum is empty for any fixed α∈(0,12) and |ß| small enough.

Pharmacodynamics and pharmacokinetics of synthetic mineralocorticoids and glucocorticoids: receptor transactivation and prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases.

Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for steroids often used in clinical practice. HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes. GC and MC transcriptional activity was tested by luciferase assay in CV-1 cells transfected with human GC or MC receptor expression vectors. The 11-hydroxy-group is necessary for GC and MC receptor transactivation. As HSD2 oxidizes 11-hydroxysteroids to inactive 11-dehydrosteroids, GC and MC activity in HSD2-expressing tissues (kidney, colon) is regulated by this enzyme. As 9alpha-fluorination (such as in 9alpha-fluorocortisol) decreases oxidation by HSD2 and increases both GC and MC receptor transactivation, this modification leads to optimal, but non-selective transactivation of both receptors. Increased GC receptor and decreased MC receptor transactivation leading to more selective GC activity is reached using the following substituents: 16beta-methyl (in betamethasone), 16alpha-methyl (in dexamethasone) and triangle up 1-dehydro-configuration (in prednisolone). Whereas the modifications in position 16 decrease oxidation by HSD2, the triangle up 1-dehydro-configuration increases HSD2-activity leading to an enhanced inactivation of prednisolone compared to all other steroids. 9alpha-fluorocortisol, the most frequently used substance for MC-substitution, seems to be the best choice of available steroids for this purpose. Whereas GC selectivity can be improved by hydrophobic substituents in position 16 and the triangle up 1-dehydro-configuration, maximal GC activity needs additional fluorination in position 9alpha (such as in dexamethasone). For GC therapy directed to HSD2-expressing organs, widely used prednisolone does not seem to be the optimal recommendation.

Differential diagnosis of polyuric/polydipsic syndromes with the aid of urinary vasopressin measurement in adults.

OBJECTIVE: A water deprivation test or a hypertonic saline infusion test with the measurement of plasma osmolality and plasma vasopressin are the gold standard tests in the differential diagnosis of polyuric syndromes. Because commercially available vasopressin kits are too insensitive for this approach, and the concentration of vasopressin in urine is much higher than in plasma, urinary vasopressin measurements may be an alternative to the more difficult plasma vasopressin measurement. DESIGN: The diagnostic value of the measurement of urinary vasopressin with a rather insensitive commercially available vasopressin kit was compared with plasma vasopressin measurement by a highly sensitive radioimmunoassay (RIA). PATIENTS AND METHODS: Thirteen normal subjects and 27 patients with polyuria/polydipsia were examined by an 8-h fluid deprivation test. In all blood samples (0800 h, 1200 h, 1400 h and 1600 h) and in all urine collections (2-hourly fractions), osmolality as well as vasopressin were measured. RESULTS: Using plasma vasopressin measurement with a highly sensitive RIA as gold standard test, nine patients were classified as having primary polydipsia, whereas 18 had partial or complete cranial diabetes insipidus. Whereas the substitution of plasma vasopressin measurement by urinary vasopressin measurement alone did not provide 100% separation between both groups, the product of urinary vasopressin and urinary osmolality related to plasma osmolality completely separated the patients with primary polydipsia from those with diabetes insipidus. Urinary measurement of vasopressin and osmolality alone, which was recommended as a noninvasive diagnostic procedure in children, was too insensitive for exact differential diagnosis in our adult patients. CONCLUSIONS: The simultaneous measurement of plasma vasopressin and plasma osmolality in a dehydration test is the most powerful diagnostic tool in the differential diagnosis of polyuria/polydipsia. However, if highly sensitive assays for plasma vasopressin measurements are not available, the measurement of urinary vasopressin with commercially available, less sensitive RIAs may be a diagnostic alternative, which showed nearly the same sensitivity as plasma vasopressin measurement in our study population.

Two-component interference effect: model of a spin-polarized transport.

The effect of spin-involved interaction on the transport properties of disordered two-dimensional electron systems with ferromagnetic contacts is described using a two-component model. Components representing spin-up and spin-down states are supposed to be coupled at a discrete set of points. We have found that due to the additional interference arising in two-component systems the difference between conductances for the parallel and antiparallel orientations of the contact magnetization changes its sign as a function of the length of the conducting channel.

Pituitary function tests: comparison of ACTH and 11-deoxy-cortisol responses in the metyrapone test and with the insulin hypoglycemia test.

PURPOSE: To compare the sensitivity of ACTH and 11-deoxy-cortisol (comp. S) responses in the short metyrapone test and the latter with the insulin hypoglycemia test. METHODS: Retrospective evaluation of 115 short metyrapone tests and comparison of 18 pairs of metyrapone and insulin tests. 20 healthy controls and 95 patients with confirmed pituitary disease were studied. All hormones were measured by sensitive radioimmunoassays. RESULTS: In patients with pituitary disease not requiring hydrocortisone substitution (n = 70), the ACTH response in the metyrapone test was subnormal in 47 cases (< 33 pmol/L), the comp. S response (< 200 nmol/L) in 21 cases only. Comparison of the relationship between ACTH and comp. S with an ACTH-cortisol dose-response curve obtained in normal subjects shows that subnormal ACTH responses after metyrapone in the range between 13 and 33 pmol/L still generate normal comp. S responses. The results of the metyrapone test correlated significantly with those of the insulin test. CONCLUSIONS: Measuring plasma ACTH in the scope of the metyrapone test makes the test more sensitive to detect secondary adrenal insufficiency than with steroid measurements alone. Results of the metyrapone test correlate significantly with the cortisol response to insulin hypoglycemia.

Effect of angiotensin II on plasma ACTH in patients with Addison's disease.

Short-term angiotensin II (AII) infusions (3 ng/kg/min) were performed in 5 patients with Addison's disease in order to assess the effect of AII on ACTH secretion. Base line ACTH levels were elevated due to a 9-h time lag between hydrocortisone administration and onset of the study. In 2 separate infusion periods of 30-min duration, AII had no unidirectional effect on plasma ACTH. Mean ACTH increased slightly but insignificantly. Mean blood pressure rose by about 10 mmHg. The degree of angiotensinaemia induced is probably similar to the state of moderate to severe sodium deficiency. Short-term changes of AII in this order of magnitude have obviously no major effect on ACTH secretion.